RT Journal
A1 Lee, Dongwon
A1 Kapoor, Ashish
A1 Lee, Changhee
A1 Mudgett, Michael
A1 Beer, Michael A.
A1 Chakravarti, Aravinda
T1 Sequence-based correction of barcode bias in massively parallel reporter assays
JF Genome Research 
JO Genome Research 
YR 2021 
FD September 01 
VO 31 
IS 9 
SP 1638 
OP 1645 
DO 10.1101/gr.268599.120 
UL http://genome.cshlp.org/content/31/9/1638.abstract 
AB Massively parallel reporter assays (MPRAs) are a high-throughput method for evaluating in vitro activities of thousands of candidate cis-regulatory elements (CREs). In these assays, candidate sequences are cloned upstream or downstream from a reporter gene tagged by unique DNA sequences. However, tag sequences may themselves affect reporter gene expression and lead to major potential biases in the measured cis-regulatory activity. Here, we present a sequence-based method for correcting tag-sequence-specific effects and show that our method can significantly reduce this source of variation and improve the identification of functional regulatory variants by MPRAs. We also show that our model captures sequence features associated with post-transcriptional regulation of mRNA. Thus, this new method helps not only to improve detection of regulatory signals in MPRA experiments but also to design better MPRA protocols.